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Molecular Cytogenetics

A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias

Leukemia volume 19, pages 358–366 (2005)Cite this article

Abstract

Chromosomal translocations with breakpoints in T-cell receptor (TCR) genes are recurrent in T-cell malignancies. These translocations involve the TCRαδ gene (14q11), the TCRβ gene (7q34) and to a lesser extent the TCRγ gene at chromosomal band 7p14 and juxtapose T-cell oncogenes next to TCR regulatory sequences leading to deregulated expression of those oncogenes. Here, we describe a new recurrent chromosomal inversion of chromosome 7, inv(7)(p15q34), in a subset of patients with T-cell acute lymphoblastic leukemia characterized by CD2 negative and CD4 positive, CD8 negative blasts. This rearrangement juxtaposes the distal part of the HOXA gene cluster on 7p15 to the TCRβ locus on 7q34. Real time quantitative PCR analysis for all HOXA genes revealed high levels of HOXA10 and HOXA11 expression in all inv(7) positive cases. This is the first report of a recurrent chromosome rearrangement targeting the HOXA gene cluster in T-cell malignancies resulting in deregulated HOXA gene expression (particularly HOXA10 and HOXA11) and is in keeping with a previous report suggesting HOXA deregulation in MLL-rearranged T- and B cell lymphoblastic leukemia as the key factor in leukaemic transformation. Finally, our observation also supports the previous suggested role of HOXA10 and HOXA11 in normal thymocyte development.

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Acknowledgements

This study was supported by the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, Grants nr. G.0310.01 and G.0106.05 and GOA, Grant nr. 12051203. BC is supported by the Belgian program of Interuniversity Poles of Attraction. JV is supported by a post-doctoral grant from the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT). NVR and JC are postdoctoral researchers and BV and PV are senior clinical investigators of the Fonds voor Wetenschappelijk Onderzoek-Vlaanderen. We are thankful to Betty Emanuel and Nurten Yigit for excellent technical assistance.

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Author notes

  1. F Speleman and B Cauwelier: Both authors contributed equally.

Authors and Affiliations

  1. Centre for Medical Genetics, Ghent University Hospital, Ghent, Belgium

    F Speleman, B Cauwelier, B Poppe, N Van Roy, J Vandesompele & A De Paepe

  2. Laboratoire d'Hématologie, Hôpital Purpan, Toulouse, France

    N Dastugue, A Robert & F Huguet

  3. Centre for Human Genetics, U.Z. Gasthuisberg, University of Leuven, Leuven, Belgium

    J Cools, P Vandenberghe, P Marynen & A Hagemeijer

  4. Department of Clinical Chemistry, Microbiology and Immunology,

    B Verhasselt

  5. Centre for Molecular Diagnostics, Ghent University Hospital, Ghent, Belgium

    F Speleman, B Cauwelier, N Dastugue, J Cools, B Verhasselt, B Poppe, N Van Roy, J Vandesompele, C Graux, A Uyttebroeck, M Boogaerts, B De Moerloose, Y Benoit, D Selleslag, J Billiet, A Robert, F Huguet, P Vandenberghe, A De Paepe, P Marynen & A Hagemeijer

  6. Department of Hematology, U.Z. Gasthuisberg, University of Leuven, Leuven, Belgium

    C Graux & M Boogaerts

  7. Department of Pediatric Hematology/Oncology, U.Z.Gasthuisberg, University of Leuven, Leuven, Belgium

    A Uyttebroeck

  8. Department of Pediatric Hematology/Oncology, Ghent University Hospital, Ghent, Belgium

    B De Moerloose & Y Benoit

  9. Department of Clinical Hematology and Clinical Biology, AZ St Jan, Bruges, Belgium

    D Selleslag & J Billiet

  10. Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium

    J Cools & P Marynen

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Correspondence to F Speleman.

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Speleman, F., Cauwelier, B., Dastugue, N. et al. A new recurrent inversion, inv(7)(p15q34), leads to transcriptional activation of HOXA10 and HOXA11 in a subset of T-cell acute lymphoblastic leukemias. Leukemia 19, 358–366 (2005). https://doi.org/10.1038/sj.leu.2403657

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